Hydrochloric Acid → 1-(2-methoxy-4-(thiazol-2-yl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Participants

Reaction Steps

A solution of PdCl2(dppf)-CH2Cl2 adduct (0.127 g, 0.156 mmol), 2-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)thiazole (Intermediate OOOOO; 0.643 g, 2.026 mmol), 1-chloro-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (Intermediate GG) (0.500 g, 1.559 mmol), and potassium carbonate (0.862 g, 6.24 mmol) in 6 mL dioxane/2 mL water was heated to 110° C. for 2 hours. LC/MS showed mostly product, so the reaction mixture was allowed to cool to room temperature. The aqueous layer was removed, and the reaction mixture was treated with HCl (4N in dioxane) (1.559 ml, 6.24 mmol). After stirring for an additional 10 minutes, the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18 30μ, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 1-(2-methoxy-4-(thiazol-2-yl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.507 g, 1.066 mmol, 68.4% yield). 1H NMR (MeCN-d3) δ: 8.71 (d, J=5.7 Hz, 1H), 8.63 (s, 1H), 8.48 (s, 1H), 8.21 (d, J=6.3 Hz, 1H), 7.91-7.97 (m, 3H), 7.75-7.84 (m, 2H), 7.72 (sd, J=7.8 Hz, 1H), 7.60 (d, J=3.2 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.06 (s, J=6.3 Hz, 1H), 3.75 (s, 3H); (M+H)+=476.0.

Provenance & Evidence